For diagnostic and therapeutic purposes, it is important to establish reliable biological markers for Alzheimer's disease (AD). Positron emission tomography (PET) was performed on 12 Alzheimer's patients (Pts) and 12 controls (NC) to measure regional cerebral blood flow (rCBF) using O15 labeled water and opiate receptor avidity (CF) using 6-deoxy-6-b-[18F]fluoronaltrexone. rCBF and CF was reduced in AD. Pts were found to have a strikingly higher MES/NEO (medial temporal lobe/ lateral temporal lobe) ratio than NC. A value of 1 for this ratio provided a highly sensitive (100%) and specific (90%) discriminant of AD. Thus, in the normal aged, the rCBF of the lateral temporal lobe is greater than that of the mesial temporal lobe while this relationship is reversed in AD. Neurodegenerative changes are the likely underlying process responsible for both the rCBF and CF changes, but differences with respect to the patterns of these losses suggest that the intermediate mechanisms leading from neurodegeneration to loss are distinct. The molecular mechanisms whereby atypical neuroleptic (AN) differ from typical neuroleptics (TN) remain elusive. [18F]-2-fluoro-2-deoxy-D-glucose (FDG) with PET was used to determine the functional pattern of metabolic activity of schizophrenic patients receiving the TN fluphenazine and the AN clozapine. The AN and TN patterns showed considerable overlap. Overall, the data suggest that neuroleptics lead to "compensation" and "adaptation" rather than a "normalization" of the functional activities of brain structures in schizophrenia, and that patients may benefit from the less powerful increase in basal ganglia and thalamic metabolic rate, and decrease in midprefrontal cortex rate induced by clozapine.